Task In Schizophrenia Research Articles

Reliability of Theory of Mind Tasks in Schizophrenia, ASD, and Nonclinical Populations: A Systematic Review and Reliability Generalization Meta-analysis.

Though theory of mind (ToM) is an important area of study for different disciplines, however, the psychometric evaluations of ToM tasks have yielded inconsistent results across studies and populations, raising the concerns about the accuracy, consistency, and generalizability of these tasks. This systematic review and meta-analysis examined the psychometric reliability of 27 distinct ToM tasks across 90 studies involving 2771 schizophrenia (SZ), 690 autism spectrum disorder (ASD), and 15,599 nonclinical populations (NC). Findings revealed that while all ToM tasks exhibited satisfactory internal consistency in ASD and SZ, about half of them were not satisfactory in NC, including the commonly used Reading the Mind in the Eye Test and Hinting Task. Other than that, Reading the Mind in the Eye Test showed acceptable reliability across populations, whereas Hinting Task had poor test-retest reliability. Notably, only Faux Pas Test and Movie for the Assessment of Social Cognition had satisfactory reliability across populations albeit limited numbers of studies. However, only ten studies examined the psychometric properties of ToM tasks in ASD adults, warranting additional evaluations. The study offered practical implications for selecting ToM tasks in research and clinical settings, and underscored the importance of having a robust psychometric reliability in ToM tasks across populations.

Suicidality, perceived chronic stress, and stress-induced cortisol changes of individuals with schizophrenia.

The associations of suicidality with stress are poorly studied in schizophrenia. The study aimed to determine whether suicidality was correlated with perceived chronic stress and the cortisol fluctuations under stress tasks in schizophrenia. High suicidality was defined as a lifetime history of suicide attempts or suicidal ideation in the past 2weeks. Individuals with schizophrenia and high suicidality (SZ-HS, n=59), with low suicidality (SZ-LS, n=207), and healthy controls (HC, n=196) finished the Perceived Stress Scale. Then, they participated in an experiment that induced stress using the Paced Auditory Serial Addition Task and the Mirror Tracing Persistence Task. Negative affect was measured at baseline and after finishing each task. The salivary cortisol was collected before-, after 20min, and after 40min of the tasks. SZ-HS had elevated perceived stress than SZ-LS and HC. Mixed effect models showed that stress tasks induced cortisol changes in all groups; cortisol of SZ-LS was reduced more than HC, but SZ-HS and SZ-LS did not differ in cortisol fluctuations. SZ-HS and SZ-LS experienced similar negative affect changes during tasks and the difference in withdrawal rates was nonsignificant. SZ-HS had an increased error rate than SZ-LS. In conclusion, suicidality was correlated with high-level perceived stress but did not result in differences in cortisol reactivities under stress tasks. It suggests the inconsistency between appraisal of stress and biological stress system disturbance among SZ-HS compared to SZ-LS.

Brain Network Localization of Gray Matter Atrophy and Neurocognitive and Social Cognitive Dysfunction in Schizophrenia

BackgroundNumerous studies have established the presence of gray matter atrophy and brain activation abnormalities during neurocognitive and social cognitive tasks in schizophrenia. Despite a growing consensus that diseases localize better to distributed brain networks than individual anatomical regions, relatively few studies have examined brain network localization of gray matter atrophy and neurocognitive and social cognitive dysfunction in schizophrenia. MethodsTo address this gap, we initially identified brain locations of structural and functional abnormalities in schizophrenia from 301 published neuroimaging studies with 8712 individuals with schizophrenia and 9275 healthy control participants. By applying novel functional connectivity network mapping to large-scale resting-state functional magnetic resonance imaging datasets, we mapped these affected brain locations to 3 brain abnormality networks of schizophrenia. ResultsThe gray matter atrophy network of schizophrenia comprised a broadly distributed set of brain areas predominantly implicating the ventral attention, somatomotor, and default networks. The neurocognitive dysfunction network was also composed of widespread brain areas primarily involving the frontoparietal and default networks. By contrast, the social cognitive dysfunction network consisted of circumscribed brain regions mainly implicating the default, subcortical, and visual networks. ConclusionsOur findings suggest shared and unique brain network substrates of gray matter atrophy and neurocognitive and social cognitive dysfunction in schizophrenia, which may not only refine the understanding of disease neuropathology from a network perspective but may also contribute to more targeted and effective treatments for impairments in different cognitive domains in schizophrenia.

Inhibition of fatty acid amide hydrolase reverses aberrant prefrontal gamma oscillations in the sub-chronic PCP model for schizophrenia.

Hypofunctioning of NMDA receptors, and the resulting shift in the balance between excitation and inhibition, is considered a key process in the pathophysiology of schizophrenia. One important manifestation of this phenomenon is changes in neural oscillations, those above 30Hz (i.e., gamma-band oscillations), in particular. Although both preclinical and clinical studies observed increased gamma activity following acute administration of NMDA receptor antagonists, the relevance of this phenomenon has been recently questioned given the reduced gamma oscillations typically observed during sensory and cognitive tasks in schizophrenia. However, there is emerging, yet contradictory, evidence for increased spontaneous gamma-band activity (i.e., at rest or under baseline conditions). Here, we use the sub-chronic phencyclidine (PCP) rat model for schizophrenia, which has been argued to model the pathophysiology of schizophrenia more closely than acute NMDA antagonism, to investigate gamma oscillations (30-100Hz) in the medial prefrontal cortex of anesthetized animals. While baseline gamma oscillations were not affected, oscillations induced by train stimulation of the posterior dorsal CA1 (pdCA1) field of the hippocampus were enhanced in PCP-treated animals (5mg/kg, twice daily for 7days, followed by a 7-day washout period). This effect was reversed by pharmacological enhancement of endocannabinoid levels via systemic administration of URB597 (0.3mg/kg), an inhibitor of the catabolic enzyme of the endocannabinoid anandamide. Intriguingly, the pharmacological blockade of CB1 receptors by AM251 unmasked a reduced gamma oscillatory activity in PCP-treated animals. The findings are consistent with the observed effects of URB597 and AM251 on behavioral deficits reminiscent of the symptoms of schizophrenia and further validate the potential for cannabinoid-based drugs as a treatment for schizophrenia.

Relation between task-related activity modulation and cortical inhibitory function in schizophrenia and healthy controls: a TMS–EEG study

Schizophrenia has been associated with a reduced task-related modulation of cortical activity assessed through electroencephalography (EEG). However, to the best of our knowledge, no study so far has assessed the underpinnings of this decreased EEG modulation in schizophrenia. A possible substrate of these findings could be a decreased inhibitory function, a replicated finding in the field. In this pilot study, our aim was to explore the association between EEG modulation during a cognitive task and the inhibitory system function in vivo in a sample including healthy controls and patients with schizophrenia. We hypothesized that the replicated decreased task-related activity modulation during a cognitive task in schizophrenia would be related to a hypofunction of the inhibitory system. For this purpose, 27 healthy controls and 22 patients with schizophrenia (including 13 first episodes) performed a 3-condition auditory oddball task from which the spectral entropy modulation was calculated. In addition, cortical reactivity—as an index of the inhibitory function—was assessed by the administration of 75 monophasic transcranial magnetic stimulation single pulses over the left dorsolateral prefrontal cortex. Our results replicated the task-related cortical activity modulation deficit in schizophrenia patients. Moreover, schizophrenia patients showed higher cortical reactivity following transcranial magnetic stimulation single pulses over the left dorsolateral prefrontal cortex compared to healthy controls. Cortical reactivity was inversely associated with EEG modulation, supporting the idea that a hypofunction of the inhibitory system could hamper the task-related modulation of EEG activity.

8. Altered Associations Between Task Ability and Dorsolateral Prefrontal Activation During a Cognitive Control Task in Schizophrenia

8. Altered Associations Between Task Ability and Dorsolateral Prefrontal Activation During a Cognitive Control Task in Schizophrenia

Decreased integration of default-mode network during a working memory task in schizophrenia with severe attention deficits.

Working memory (WM) and attention deficits are both important features of schizophrenia. WM is closely related to attention, for it acted as an important characteristic in activating and manipulating WM. However, the knowledge of neural mechanisms underlying the relationship between WM and attention deficits in schizophrenia is poorly investigated. Graph theory was used to examine the network topology at the whole-brain and large-scale network levels among 125 schizophrenia patients with different severity of attention deficits (65 mild attention deficits; 46 moderate attention deficits; and 14 severe attention deficits) and 53 healthy controls (HCs) during an N-back WM task. These analyses were repeated in the same participants during the resting state. In the WM task, there were omnibus differences in small-worldness and normalized clustering coefficient at a whole-brain level and normalized characterized path length of the default-mode network (DMN) among all groups. Post hoc analysis further indicated that all patient groups showed increased small-worldness and normalized clustering coefficient of the whole brain compared with HCs, and schizophrenia with severe attention deficits showed increased normalized characterized path length of the DMN compared with schizophrenia with mild attention deficits and HCs. However, these observations were not persisted under the resting state. Further correlation analyses indicated that the increased normalized characterized path length of the DMN was correlated with more severe attentional deficits and poorer accuracy of the WM task. Our research demonstrated that, compared with the schizophrenia patients with less attention deficits, disrupted integration of the DMN may more particularly underlie the WM deficits in schizophrenia patients with severe attention deficits.

Vergence eye movements impairments in schizophrenia and bipolar disorder

One of the most evaluated eye tracking tasks in schizophrenia (SZ) and bipolar disorder (BD) are smooth pursuit eye movements. They rely on the maintenance of slowly moving object on the fovea. While most of the studies evaluated tracking of a target that moves in the fronto-parallel plane, only two assessed vergence eye movements (VEM), which relies on the pursuit of object that moves in depth. The aim of our study was to compare VEM performance in SZ and BD. We evaluated 28 SZ patients, 32 BD patients and 25 healthy controls (HC). Participants underwent thorough optometric examination before eye tracking task. VEM were measured with the use of infrared eye tracker and dedicated vergence stimuli generator. SZ patients showed higher mean break and recovery points of fusion and shorter correct tracking time than HC. BD individuals revealed tracking accuracy deficits and higher number of saccades than HC. Compared to BD, SZ patients showed decrease of maximal convergence and divergence. Moreover, they presented tracking accuracy deficits of non-dominant eye: altered eyes positioning error during convergence and divergence gain. Exploratory analysis revealed significant gender differences between groups in terms of binocular VEM parameters. In this study we have recognized pattern of eye movement disturbances differentiating abovementioned groups. SZ patients showed decreased vergence tracking range with shorter tracking time and impaired accuracy of non-dominant eye, while BD patients showed higher number of saccades with decreased tracking accuracy. Neuroimaging studies are necessary to identify neuronal underpinnings of VEM impairments in SZ and BD.

Reorganization of the functional connectome from rest to a visual perception task in schizophrenia and bipolar disorder

Functional connectome organization is altered in schizophrenia (SZ) and bipolar disorder (BD). However, it remains unclear whether network reorganization during a task relative to rest is also altered in these disorders.This study examined connectome organization in patients with SZ (N = 43) and BD (N = 42) versus healthy controls (HC; N = 39) using fMRI data during a visual object-perception task and at rest. Graph analyses were conducted for the whole-brain network using indices selected a priori: three reflecting network segregation (clustering coefficient, local efficiency, modularity), two reflecting integration (characteristic path length, global efficiency).Group differences were limited to network segregation and were more evident in SZ (clustering coefficient, modularity) than in BD (clustering coefficient) compared to HC. State differences were found across groups for segregation (local efficiency) and integration (characteristic path length). There was no group-by-state interaction for any graph index.In summary, aberrant network organization compared to HC was confirmed, and was more evident in SZ than in BD. Yet, reorganization was largely intact in both disorders. These findings help to constrain models of dysconnection in SZ and BD, suggesting that the extent of functional dysconnectivity in these disorders tends to persist across changes in mental state.

Spectral perturbations of cortical dipoles during a dynamic visuo-spatial working memory task in schizophrenia

Altered neural oscillations during prestimulus-task conditions have been reported to be associated with aberrant information processing in schizophrenia. Spectral perturbations induced by visuo-spatial working memory (VSWM) task were investigated in patients and their first-degree relatives in order to study the biomarkers in schizophrenia. EEG was recorded using 128-channel during VSWM task in 28 patients, 27 first-degree relatives and 25 controls. After pre-processing and ICA, current dipole was estimated for each IC. Total of 1609 independent and localizable EEG components across all groups were used to compute ERSP during different events of task. Patients deactivated DMN, RSN, auditory cortex more compared to controls during search period to perform VSWM task. Relatives showed altered activation of right medial and inferior frontal gyri during different events and loads of task in lower frequencies compared to controls. Relatives also showed hyperactivity in right cingulate and parahippocampal gyri compared to controls. This is suggestive of genetic predisposition in schizophrenia and could act as vulnerability markers, further strengthened by no significant differences between patients and relatives. Altered processing of simultaneous ongoing events in patients and relatives can serve as state and trait-specific features of schizophrenia.

P558. Alpha Phase Coherence and Desynchronization During the Degraded-Stimulus Continuous Performance Task in Schizophrenia

Alpha oscillations are relevant to visual perceptual processes that support attention and higher-order cognition. Our previous work demonstrated that resting state alpha peak frequencies were slower in schizophrenia, and corresponded to impairments on a visual attention task (Degraded-Stimulus Continuous Performance Task; DS-CPT). In the current study we examine EEG during the DS-CPT to clarify whether alpha phase coherence and synchronization are aberrant during visual attention.

Relation between EEG resting-state power and modulation of P300 task-related activity in theta band in schizophrenia

There is some consistency in previous EEG findings that patients with schizophrenia have increased resting-state cortical activity. Furthermore, in previous work, we have provided evidence that there is a deficit in the modulation of bioelectrical activity during the performance of a P300 task in schizophrenia. Our hypothesis here is that a basal hyperactivation would be related with altered ability to change or modulate cortical activity during a cognitive task. However, no study so far, to the best of our knowledge, has studied the association between resting-state activity and task-related modulation. With this aim, we used a dual EEG paradigm (resting state and oddball task for elicitation of the P300 evoked potential) in a sample of patients with schizophrenia (n = 100), which included a subgroup of patients with first episode psychosis (n = 30), as well as a group of healthy controls (n = 93). The study measures were absolute power for resting-state; and spectral entropy (SE) and connectivity strength (CS) for P300-task data, whose modulation had been previously found to be altered in schizophrenia. Following the literature on P300, we focused our study on the theta frequency band. As expected, our results showed an increase in resting state activity and altered task-related modulation. Moreover, we found an inverse relationship between the amount of resting-state activity and modulation of task-related activity. Our results confirm our hypothesis and support the idea that a greater amount of resting theta-band synchrony could hamper the modulation of signal regularity (quantified by SE) and activity density (measured by CS) during the P300 task performance. This association was found in both patients and controls, suggesting the existence of a common mechanism and a possible ceiling effect in schizophrenia patients in relation to a decreased inhibitory function that limits their cortical reactivity to the task.

The association between resting-state eeg activity and the ability to modulate cortical activity during a cognitive task in schizophrenia

The association between resting-state eeg activity and the ability to modulate cortical activity during a cognitive task in schizophrenia

Paliperidone Compared with Haloperidol on the Theory of Mind Tasks in Schizophrenia: A Pilot Trial.

PurposeTheory of mind (ToM) is an important part of social cognitive function and is associated with medial prefrontal cortical (mPFC) activity. This study aimed to evaluate the efficacy of paliperidone in improving ToM task performance in patients with schizophrenia compared with haloperidol.Patients and MethodsThis study was a single-center, single-blinded (assessor), parallel-group randomized clinical trial of patients with schizophrenia randomized to paliperidone or haloperidol. ToM was assessed at weeks 0, 8, 12, and 16 using the first-order belief, higher-order belief, faux-pas, and Reading the Mind in the Eyes tests. The primary outcome was the change in the ToM performance scores from baseline to after 16 weeks of treatment.ResultsThe participants received paliperidone (n = 29) or haloperidol (n = 31). For the first-order belief task, there were no between-group differences (P > 0.05) but time differences in both groups (P < 0.05). For the higher-order belief task, there were no between-group differences (P > 0.05), but there were time differences in both groups (P < 0.05) and a time×group interaction in the paliperidone group only (P < 0.05). For the faux-pas task, there was a difference between groups at week 16 (P < 0.05), and the improvement in time was significant for the paliperidone group only (P < 0.05). For the Reading the Mind in the Eyes task, there was an improvement over time for the paliperidone group only (P < 0.05). Safety was manageable in both groups.ConclusionPaliperidone treatment might be more effective than haloperidol in improving ToM task performance in schizophrenia.Trial Registrationchictr.org.cn_identifier ChiCTR-IPR-15007635.

Prefrontal Cortex Activation During Verbal Fluency Task and Tower of London Task in Schizophrenia and Major Depressive Disorder.

Background: Cognitive dysfunction is a common clinical feature of mental disorders. A number of functional near-infrared spectroscopy (fNIRS) studies have shown reduced prefrontal activation during the verbal fluency task (VFT) in schizophrenia (SZ) and major depressive disorder (MDD). However, no studies have examined and compared the brain activation patterns during the Tower of London (TOL), which is another classic, high-sensitivity executive function testing tool, in these two serious mental disorders. This study aimed to assess the characteristics of brain activation during the two different cognitive tasks in SZ and MDD patients.Methods: This study recruited 30 patients with SZ, 30 patients with MDD, and 30 demographically matched healthy controls (HCs). The hemodynamic changes of the prefrontal cortex (PFC) were measured using 32-channel fNIRS during performance of the TOL task and VFT task.Results: SZ patients showed poorer VFT performance than MDD patients and HCs, and the two patient groups showed poorer TOL performance than HCs. Compared to HCs, both of the patient groups exhibited a significant decreased activation in the extensive PFC. Particularly in certain channels in the dorsolateral PFC (DLPFC), SZ patients exhibited significantly decreased hemodynamic changes than the MDD patients.Conclusions: Patients with SZ and MDD have different levels of impairment in different cognitive domains and different patterns of brain activation during the two cognitive tasks. Further research is needed to determine the use of fNIRS for clinical evaluation and diagnosis.

Relationships Between Reward-Based Decision Making and Activation in a Frontal-Striatal Network in Schizophrenia vs. Bipolar Disorder

The contributions of brain activity to altered behavioral decision-making during reward in schizophrenia (SZ) and bipolar disorder (BD) are poorly understood. Here we examined relationships between parameters in the drift diffusion model (DDM) of decision making and brain activation in frontal and striatal brain areas during the incentivized control engagement task in schizophrenia (SZ) and bipolar disorder (BD).

Prefrontal cortex activation during working memory task in schizophrenia: A fNIRS study.

Neurocognitive cognitive deficits including working memory (WM) impairment is a key component of schizophrenia (SCZ). Though a prefrontal cortex (PFC) abnormality is recognised to contribute to WM impairment, the exact nature of its neurobiological basis in SCZ is not well established. Functional near infra-red spectroscopy (fNIRS) is an emerging low-cost neuroimaging tool to study neuro-hemodynamics. In this background, we examined the hemodynamic activity during a WM task in schizophrenia using fNIRS. fNIRS was acquired during computerised N-back (zero-, one- & two-back) task in 15 SCZ patients and compared with 22 healthy controls. Performance in N-back test were calculated using signal detection theory alongside the mean reaction times. Concentration and latencies of oxy-, deoxy-, and totalhaemoglobin, and oxygen saturation were computed from 8*8 optodes positioned over bilateral PFC. SCZ performed poorly as measured by most of the WM parameters (p < 0.05). Lesser deoxyhemoglobin concentration (two > zero, at right BA10, p = 0.006) was noted in the right frontopolar cortex in SCZ surviving multiple-comparison correction. In addition, olanzapine equivalent doses correlated negatively with right frontopolar cortex activation (two > zero back, BA10, ρ = 0.70, p = 0.004) and better performance in two back (false alarm rate, ρ = 0.61, p = 0.015). A delayed but compensatory hyperactivation of right frontopolar cortex noted in SCZ may underlie the WM deficit in SCZ. Future studies are recommended to replicate the role of right frontopolar cortex in WM using larger samples and systematically explore the effect of antipsychotics on them.

Dynamic Changes of Brain Networks during Working Memory Tasks in Schizophrenia

Electroencephalograph (EEG) signals and graph theory measures have been widely used to characterize the brain functional networks of healthy individuals and patients by calculating the correlations between different electrodes over an entire time series. Although EEG signals have a high temporal resolution and can provide relatively stable results, the process of constructing and analyzing brain functional networks is inevitably complicated by high time complexity. Our goal in this research was to distinguish the brain function networks of schizophrenia patients from those of healthy participants during working memory tasks. Consequently, we utilized a method involving microstates, which are each characterized by a unique topography of electric potentials over an entire channel array, to reduce the dimension of the EEG signals during working memory tasks and then compared and analyzed the brain functional networks using the microstates time series (MTS) and original time series (OTS) of the schizophrenia patients and healthy individuals. We found that the right frontal and parietal-occipital regions neurons of the schizophrenia patients were less active than those of the healthy participants during working memory tasks. Notably, compared with OTS, the time needed to construct the brain functional networks was significantly reduced by using MTS. In conclusion, our results show that, like OTS, MTS can well distinguish the brain functional network of schizophrenia patients from those of healthy individuals during working memory tasks while greatly decreasing time complexity. MTS can thus provide a method for characterizing the original time series for the construction and analysis of EEG brain functional networks.

Auditory paired-stimuli responses across the psychosis and bipolar spectrum and their relationship to clinical features.

EEG responses during auditory paired-stimuli paradigms are putative biomarkers of psychosis syndromes. The initial iteration of the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP1) showed unique and common patterns of abnormalities across schizophrenia (SZ), schizoaffective disorder (SAD), and bipolar disorder with psychosis (BDP). This study replicates those findings in new and large samples of psychosis cases and extends them to an important comparison group, bipolar disorder without psychosis (BDNP). Paired stimuli responses from 64-sensor EEG recording were compared across psychosis (n = 597; SZ = 225, SAD = 201, BDP = 171), BDNP (n = 66), and healthy (n = 415) subjects from the second iteration of B-SNIP. EEG activity was analyzed in voltage and in the time-frequency domain. Principal component analysis (PCA) over sensors (sPCA) was used to efficiently capture EEG voltage responses to the paired stimuli. Evoked power was calculated via a Morlet wavelet procedure. A frequency PCA divided evoked power data into three frequency bands: Low (4-17 Hz), Beta (18-32 Hz), and Gamma (33-55 Hz). Each time-course (ERP Voltage, Low, Beta, and Gamma) were then segmented into 20 ms bins and analyzed for group differences. To efficiently summarize the multiple EEG components that best captured group differences we used multivariate discriminant and correlational analyses. This approach yields a reduced set of measures that may be useful in subsequent biomarker investigations. Group ANOVAs identified 17 time-ranges that showed significant group differences (p < .05 after FDR correction), constructively replicating B-SNIP1 findings. Multivariate linear discriminant analysis parsimoniously selected variables that best accounted for group differences: The P50 response to S1 and S2 uniquely separated BDNP from healthy and psychosis subjects (BDNP > all other groups); the S1 N100 response separated groups along an axis of psychopathology severity (HC > BDNP > BDP > SAD > SZ); the S1 P200 response indexed psychosis psychopathology (HC/BDNP > SAD/SZ/BDP); and the preparatory period to the S2 stimulus separated SZ from other groups (SZ > SAD/BDP>HC/BDNP).Canonical correlation identified an association between the neural responses during the S1 N100, S1 N200 and S2 preparatory period and PANSS positive symptoms and social functioning. The neural responses during the S1 P50 and S1 N100 were associated with PANSS Negative/General, MADRS and Young Mania symptoms. This study constructively replicated prior B-SNIP1 research on auditory deviations observed during the paired stimuli task in SZ, SAD and BDP. Inclusion of a group of BDNP allows for the identification of biomarkers more closely related to affective versus nonaffective clinical phenotypes and neural distinctions between BDP and BDNP. Findings have implications for nosology and future translational work given that some biomarkers are shared across all psychosis and some are unique to affective syndromes.

Pupillary change on a cognitive effort task in schizophrenia: Associations with cognition and motivation

Motivational negative symptoms in schizophrenia are associated with abnormalities in effort allocation. Pupillary dilation is a reliable biomarker of effort allocation and was used in this study to evaluate the associations between cognitive effort, ability, and motivation. Individuals with schizophrenia/schizoaffective disorder and moderate-to-high negative symptoms were assessed with pupillometry while performing a cognitive effort task that manipulated level of cognitive difficulty. Participants were also assessed with measures of ability (i.e., cognition and functional capacity), and motivation (i.e., defeatist beliefs and motivational negative symptoms). Pupillary change was examined as an effort modulation index in relation to the ability and motivation measures. Greater pupillary change (i.e., exerting greater amounts of effort) on the hard versus easy conditions was correlated with better cognition and functional capacity and lower motivational negative symptoms, while defeatist beliefs were not significantly correlated. In hierarchical regression analyses, ability measures were entered first and motivation measures were entered second. Motivation measures predicted variance beyond ability. Our findings indicate that both ability and motivation are significant determinants of pupillary indicators of cognitive effort exertion. Further, the results highlight the importance of controlling for cognition when using pupil dilation to index effort/motivation.